Among the secreted proteins that were positively associated with executive function (p < 0.05, Fig. 3F), APOA4, LUM, and CLU are reported to be expressed in the brain (46, 47), and lower circulating abundance of APOA4 and CLU in circulation has been observed in individuals with mild cognitive impairment and Alzheimer’s Disease (48, 49), collectively suggesting that these secreted proteins may contribute to better cognitive functions. The gene discussed is CLU; the disease is early-onset autosomal dominant Alzheimer disease.